PT  - JOURNAL ARTICLE
AU  - Henrik Watz
AU  - Johannes Nagelschmitz
AU  - Frauke Pedersen
AU  - Felix C. Ringshausen
AU  - Anne Kirsten
AU  - Helgo Magnussen
AU  - Klaus F. Rabe
AU  - Tobias Welte
AU  - Jessica Rademacher
AU  - Christine Rentzsch
AU  - Christian Schumann
AU  - Dmitry Zubov
AU  - Volkhart Li
AU  - Anja Schäfer
AU  - Stephan Schwers
TI  - Conduct of a biomarker study in bronchiectasis patients: Correlation of neutrophil elastase activity and inflammatory load in induced sputum
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P2049
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P2049.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P2049.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases like bronchiectasis (BE) and COPD. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic target.In order to assess, whether biomarkers could support clinical evaluation of this new treatment concept, a multicenter biomarker study was conducted in BE patients and healthy controls: A sputum induction and processing protocol was implemented at three study sites and collected sputum was analyzed for neutrophil cell count, HNE activity, IL-8 and other markers with a 2 week interval over six weeks. In addition, the elastin degradation product desmosine was analyzed in urine.First results from 15 patients and 5 healthy controls indicate that, based on sputum HNE activity, BE patients could be divided into HNE(low) and HNE(high) groups (>10-fold difference), whereas healthy volunteers were always found to be HNE(low). Furthermore, high sputum HNE activity often coincides with other markers of inflammation (neutrophil cell count, IL-8). Those markers may guide patient selection and contribute to identifying BE patients eligible to treatment with a novel HNE inhibitor, which is currently in clinical development.In summary, Biomarker evaluation in BE patients revealed that significant HNE activity in sputum could be detected and might be used for stratification of patients for HNE inhibitor treatment.